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[PMID]: 29412223 [Au] Autor: Genari B; Leitune VCB; Jornada DS; Aldrigui BR; Pohlmann AR; Guterres SS; Samuel SMW; Collares FM [Ad] Endereço: Universidade Federal do Rio Grande do Sul - UFRGS, School of Dentistry, Dental Materials Laboratory, Porto Alegre, RS, Brazil. [Ti] Título: Effect on adhesion of a nanocapsules-loaded adhesive system. [So] Source: Braz Oral Res;32:e008, 2018 Feb 01. [Is] ISSN: 1807-3107 [Cp] País de publicação: Brazil [La] Idioma: eng [Ab] Resumo: This study aimed to evaluate the in situ degree of conversion, contact angle, and immediate and long-term bond strengths of a commercial primer and an experimental adhesive containing indomethacin- and triclosan-loaded nanocapsules (NCs). The indomethacin- and triclosan-loaded NCs, which promote anti-inflammatory and antibacterial effects through controlled release, were incorporated into the primer at a concentration of 2% and in the adhesive at concentrations of 1, 2, 5, and 10%. The in situ degree of conversion (DC, n=3) was evaluated by micro-Raman spectroscopy. The contact angle of the primer and adhesive on the dentin surface (n = 3) was determined by an optical tensiometer. For the microtensile bond strength µTBS test (12 teeth per group), stick-shaped specimens were tested under tensile stress immediately after preparation and after storage in water for 1 year. The data were analyzed using two-way ANOVA, three-way ANOVA and Tukey's post hoc tests with α=0.05. The use of the NC-loaded adhesive resulted in a higher in situ degree of conversion. The DC values varied from 75.07 ± 8.83% to 96.18 ± 0.87%. The use of NCs in only the adhesive up to a concentration of 5% had no influence on the bond strength. The contact angle of the primer remained the same with and without NCs. The use of both the primer and adhesive with NCs (for all concentrations) resulted in a higher contact angle of the adhesive. The longitudinal µTBS was inversely proportional to the concentration of NCs in the adhesive system, exhibiting decreasing values for the groups with primer containing NCs and adhesives with increasing concentrations of NCs. Adhesives containing up to 5% of nanocapsules and primer with no NCs maintained the in situ degree of conversion, contact angle, and immediate and long-term bond strengths. Therefore, the NC-loaded adhesive can be an alternative method for combining the bond performance and therapeutic effects. The use of an adhesive with up to 5% nanocapsules containing indomethacin and triclosan and a primer with no nanocapsules maintained the long-term bond performance. [Mh] Termos MeSH primário: Colagem Dentária/métodos Indometacina/química Nanocápsulas/química Cimentos de Resina/química Triclosan/química [Mh] Termos MeSH secundário: Análise de Variância Animais Bovinos Falha de Restauração Dentária Dentina/efeitos dos fármacos Teste de Materiais Transição de Fase/efeitos dos fármacos Polimerização/efeitos dos fármacos Valores de Referência Reprodutibilidade dos Testes Análise Espectral Raman Propriedades de Superfície/efeitos dos fármacos Resistência à Tração Fatores de Tempo [Pt] Tipo de publicação: EVALUATION STUDIES; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Nanocapsules); 0 (Resin Cements); 4NM5039Y5X (Triclosan); 90881-69-9 (Scotchbond); XXE1CET956 (Indomethacin) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180307 [Lr] Data última revisão: 180307 [Sb] Subgrupo de revista: D; IM [Da] Data de entrada para processamento: 180208 [St] Status: MEDLINE

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[PMID]: 29465556 [Au] Autor: Ni Y; Jiang C [Ad] Endereço: Department of Spine Surgery. [Ti] Título: Identification of potential target genes for ankylosing spondylitis treatment. [So] Source: Medicine (Baltimore);97(8):e9760, 2018 Feb. [Is] ISSN: 1536-5964 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: This study aimed to identify the potential target genes for the treatment of ankylosing spondylitis (AS).Dataset GSE25101 was downloaded from Gene Expression Omnibus, including 16 AS and 16 normal control blood samples. Differentially expressed genes (DEGs) were identified using unmatched t-test in limma package with adjusted P < .05. Gene ontology-biological process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using multifaceted analysis tool for human transcriptome. Protein-protein interaction (PPI) network was constructed using STRING and Cytoscape, and module analysis was performed using MCODE plug-in. Webgestal was utilized to predict transcriptional factor (TF)-microRNA-target network and Comparative Toxicogenomics Database (CTD) was applied to predict chemical-target network.A total of 334 DEGs were identified, including 136 upregulated genes and 198 downregulated genes. According to STRING, a PPI network was constructed and 1 significant clustered module was screen out with score = 6.33. MAPK7 (degree = 11) and NDUFS4 (degree = 10) were 2 important nodes in PPI network, and both of them were significantly enriched in cAMP mediated signaling pathway (P = 2.02E-02). MAPK7 could be regulated by NFY. Both MAPK7 and NDUFS4 were 2 potential targets for Indomethacin.MAPK7 and NDUFS4 played important roles in the pathogenesis of AS via cAMP mediated signaling pathway. Both of them could be targeted by Indomethacin. [Mh] Termos MeSH primário: Proteína Quinase 7 Ativada por Mitógeno/sangue NADH Desidrogenase/sangue Mapeamento de Interação de Proteínas/métodos Mapas de Interação de Proteínas/genética Espondilite Anquilosante/genética [Mh] Termos MeSH secundário: Anti-Inflamatórios não Esteroides/farmacologia Estudos de Casos e Controles Análise por Conglomerados Biologia Computacional Redes Reguladoras de Genes Seres Humanos Indometacina/farmacologia Transdução de Sinais/genética Espondilite Anquilosante/sangue Espondilite Anquilosante/tratamento farmacológico Transcriptoma [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anti-Inflammatory Agents, Non-Steroidal); EC 1.6.5.3 (NDUFS4 protein, human); EC 1.6.99.3 (NADH Dehydrogenase); EC 2.7.11.24 (MAPK7 protein, human); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 7); XXE1CET956 (Indomethacin) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180302 [Lr] Data última revisão: 180302 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 180222 [St] Status: MEDLINE [do] DOI: 10.1097/MD.0000000000009760

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[PMID]: 28456771 [Au] Autor: Kim EK; Cho JH; Jeong AR; Kim EJ; Park DK; Kwon KA; Chung JW; Kim KO; Kim JH; Kim JH; Kim YJ [Ad] Endereço: Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea. yoonmed@gilhospital.com. [Ti] Título: Anti-inflammatory effects of simvastatin in nonsteroidal anti-inflammatory drugs-induced small bowel injury. [So] Source: J Physiol Pharmacol;68(1):69-77, 2017 Feb. [Is] ISSN: 1899-1505 [Cp] País de publicação: Poland [La] Idioma: eng [Ab] Resumo: Small bowel injury can occur as the result of a multifaceted process that includes increased acid secretion, generation of reactive oxygen species, and cyclooxygenase inhibition. However, no effective medication for small bowel ulceration is available. Simvastatin is an important lipid-lowering agent with anti-inflammatory activity. We aimed to validate the effects of simvastatin in vitro and in vivo. In presence or absence of simvastatin, IEC-6 small bowel cell line with 50 ng/ml of tumor nectosis factor α (TNF-α) was investigated by western blotting, qRT-PCR, and DCF-DA assay. In addition, an in vivo study of nonsteroidal anti-inflammatory drugs (NSAID)-induced small bowel inflammation was performed using 7-week-old specific-pathogen-free (SPF) male C57BL/6 mice. Simvastatin treatment reduced the mRNA levels of interleukin-6 and interleukin-8 by approximately 50% in TNF-α-stimulated IEC-6 cells. Treatment with a combination of 50 ng/ml TNF-α and µM simvastatin decreased activation of Akt, IκBα, and nuclear factor-κB p65 level in IEC-6 cells. By DCF-DA staining, intracellular reactive oxygen species (ROS) production was increased in TNF-α-stimulated cells, and treatment with simvastatin decreased the level of ROS. In addition, in vivo mouse model of NSAID-induced small bowel inflammation, the administration of simvastatin reduced the number of small bowel hemorrhagic lesions and the level of ROS production as determined by gross examination and 8-hydroxydeoxyguanosine immunohistochemistry of small bowel tissue, respectively. Simvastatin reduced NSAID-induced injuries by both suppression of ROS generation and modulation of inflammatory cytokines in vitro and in vivo. Therefore, simvastatin, an HMG-CoA reductase inhibitor, has potential as a prophylactic and therapeutic agent for NSAID-induced small bowel injury. [Mh] Termos MeSH primário: Anti-Inflamatórios/efeitos adversos Anti-Inflamatórios/uso terapêutico Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico Indometacina/efeitos adversos Enteropatias/tratamento farmacológico Intestino Delgado/lesões Sinvastatina/uso terapêutico [Mh] Termos MeSH secundário: Animais Linhagem Celular Ciclo-Oxigenase 1/genética Ciclo-Oxigenase 2/genética Desoxiguanosina/análogos & derivados Desoxiguanosina/metabolismo Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia Interleucina-6/metabolismo Interleucina-8/metabolismo Enteropatias/induzido quimicamente Enteropatias/metabolismo Enteropatias/patologia Intestino Delgado/metabolismo Intestino Delgado/patologia Masculino Proteínas de Membrana/genética Camundongos Endogâmicos C57BL Inibidor de NF-kappaB alfa/metabolismo Ratos Espécies Reativas de Oxigênio/metabolismo Sinvastatina/farmacologia Fator de Necrose Tumoral alfa/metabolismo Fator de Necrose Tumoral alfa/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anti-Inflammatory Agents); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); 0 (Interleukin-6); 0 (Interleukin-8); 0 (Membrane Proteins); 0 (Reactive Oxygen Species); 0 (Tumor Necrosis Factor-alpha); 139874-52-5 (NF-KappaB Inhibitor alpha); 88847-89-6 (8-oxo-7-hydrodeoxyguanosine); AGG2FN16EV (Simvastatin); EC 1.14.99.1 (Cyclooxygenase 1); EC 1.14.99.1 (Cyclooxygenase 2); EC 1.14.99.1 (Ptgs1 protein, rat); EC 1.14.99.1 (Ptgs2 protein, rat); G9481N71RO (Deoxyguanosine); XXE1CET956 (Indomethacin) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180220 [Lr] Data última revisão: 180220 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170501 [St] Status: MEDLINE

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[PMID]: 28454506 [Au] Autor: Pandey A; Kaushik A; Wanjari M; Dey YN; Jaiswal BS; Dhodi A [Ad] Endereço: a Department of Pharmaceutical Sciences , IFTM University , Moradabad , India. [Ti] Título: Antioxidant and anti-inflammatory activities of Aerva pseudotomentosa leaves. [So] Source: Pharm Biol;55(1):1688-1697, 2017 12. [Is] ISSN: 1744-5116 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: CONTEXT: Aerva pseudotomentosa Blatt. & Hallb. (Amaranthaceae), commonly called "Bui";, is a medicinal plant of the arid region. It is used for the treatment of inflammatory disorders, such as rheumatic pain, and healing of wounds, which are associated with oxidative stress. OBJECTIVE: The present study evaluated the antioxidant potential of Aerva pseudotomentosa leaves by in vitro models and its anti-inflammatory effect in rats. MATERIAL AND METHODS: The aqueous extract (APAE) was analyzed by HPTLC and HPLC. The antioxidant effect of APAE was evaluated by various in vitro methods [DPPH (1, 1-diphenyl-2-picryl-hydrazil) and hydrogen peroxide free radical scavenging, reducing power, and anti-lipid peroxidation assays]. Anti-inflammatory effect was studied in carrageenan and formalin-induced paw oedema models in rats. APAE (200 and 400 mg/kg) and standard drug, indomethacin (10 mg/kg), were administered orally 1 h before carrageenan/formalin administration and inflammation was noted up to 5 h. RESULTS: HPLC analysis of APAE revealed the presence of rutin. APAE showed significant scavenging effect on DPPH (IC 49.37 µ g/mL) and peroxide (IC 288.2 µ g/mL) radicals. The extract exhibited reducing potential and inhibition of lipid peroxidation. APAE treatment significantly attenuated mean increase in paw volume and exhibited inhibition of paw oedema in both in vivo models with inhibition of 45.11% and 49.42%, respectively at 5 h. DISCUSSION AND CONCLUSION: APAE exhibited in vitro antioxidant and anti-inflammatory activities. Anti-inflammatory effect of APAE may be attributed to its antioxidant potential, due to the presence of rutin and other phenolics. This study substantiates folk use of leaves in inflammatory disorders. [Mh] Termos MeSH primário: Amaranthaceae/química Anti-Inflamatórios/farmacologia Antioxidantes/farmacologia Extratos Vegetais/farmacologia [Mh] Termos MeSH secundário: Animais Anti-Inflamatórios/administração & dosagem Anti-Inflamatórios/isolamento & purificação Antioxidantes/administração & dosagem Antioxidantes/isolamento & purificação Cromatografia Líquida de Alta Pressão Modelos Animais de Doenças Relação Dose-Resposta a Droga Edema/tratamento farmacológico Edema/patologia Feminino Indometacina/farmacologia Inflamação/tratamento farmacológico Inflamação/patologia Peroxidação de Lipídeos/efeitos dos fármacos Masculino Estresse Oxidativo/efeitos dos fármacos Fenóis/isolamento & purificação Fenóis/farmacologia Folhas de Planta Ratos Ratos Wistar Rutina/isolamento & purificação Rutina/farmacologia [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anti-Inflammatory Agents); 0 (Antioxidants); 0 (Phenols); 0 (Plant Extracts); 5G06TVY3R7 (Rutin); XXE1CET956 (Indomethacin) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 180212 [Lr] Data última revisão: 180212 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170430 [St] Status: MEDLINE [do] DOI: 10.1080/13880209.2017.1321022

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[PMID]: 28450774 [Au] Autor: Akinbo F; Eze G [Ad] Endereço: Department of Medical Laboratory Science, University of Benin, Benin City, Nigeria. [Ti] Título: Combined Effects of Medicinal Plants on Induced Upper Gastrointestinal Tract Injury in Wistar Rats. [So] Source: Ethiop J Health Sci;26(6):573-580, 2016 Nov. [Is] ISSN: 2413-7170 [Cp] País de publicação: Ethiopia [La] Idioma: eng [Ab] Resumo: BACKGROUND: Herbal medicines are now recently used as treatment options. This study was conducted to determine the effect of the combination therapy of medicinal herbs in the treatment of induced gastrointestinal injury among albino wistar rats. METHODS: A total of 60 Albino Wistar rats of both sexes weighing between 130g-150g were used. The control groups which consisted of negative control groups received 1ml of normal saline while the positive control group was given 20mg/kg of indomethacin and sacrificed after 6 hours. Those in the test group were given 20mg/kg of indomethacin, treated in different doses of single and combined extracts of Allium sativum, Brassica oleracea and Aloe barbadensis at 100mg/kg, 200mg/kg and 300mg/kg body weights, twice daily for 8 days and sacrificed. RESULTS: There was no visible sign of ulceration or perforation observed on the stomach and duodenum when compared with the control. The combination of all three plant extracts at different concentrations ranging from 100 - 300mg/kg cleared all visible ulcers and perforations on the stomach of wistar rats. Similarly, all ulcers in the duodenum of indomethacin induced wistar rats were cleared by the combination of the three extracts. The sections of rat stomach and duodenum given 100mg/kg herbal cocktail and indomethacin showed normal mucosa. CONCLUSIONS: A mixture of the three herbs at 300mg/kg was better in healing gastric and duodenal ulcers. The mixture of the three plants extracts exhibit good anti-ulcer activity that warrants further studies. [Mh] Termos MeSH primário: Úlcera Duodenal/tratamento farmacológico Extratos Vegetais/farmacologia Plantas Medicinais Úlcera Gástrica/tratamento farmacológico [Mh] Termos MeSH secundário: Aloe Animais Brassica Relação Dose-Resposta a Droga Úlcera Duodenal/patologia Feminino Alho Indometacina/farmacologia Masculino Extratos Vegetais/administração & dosagem Ratos Ratos Wistar Úlcera Gástrica/patologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Plant Extracts); XXE1CET956 (Indomethacin) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180205 [Lr] Data última revisão: 180205 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170429 [St] Status: MEDLINE

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[PMID]: 29337669 [Au] Autor: Kim JI; Park SW; Lim JJ; Sohn SI; Shin JS; Park SC; Jang YP; Chung EK; Lee HW; Lee KT [Ad] Endereço: 1Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro Dongdaemun-gu, Seoul, 02447, Korea Republic of. [Ti] Título: Gastroprotective effects of the isopropanol extract of Artemisia princeps and its gastroretentive floating tablets on gastric mucosal injury. [So] Source: Acta Pharm;67(4):479-494, 2017 Dec 20. [Is] ISSN: 1846-9558 [Cp] País de publicação: Croatia [La] Idioma: eng [Ab] Resumo: In this study, we investigated the gastroprotective effect of an isopropanol extract from the aerial parts of Artemisia princeps (IPAP) and developed a gastroretentive floating tablet of IPAP (IPAP-FR) for maximized local gastroprotective effects. Pre-treatment with IPAP ameliorated the gastric mucosal hemorrhagic lesions in ethanol/HCl- or indomethacin- treated rats. IPAP decreased mucosal hemorrhage of gastric ulcers induced by ethanol or indomethacin plus pyloric ligation in rats. The optimized floating tablet, IPAP-FR, floated on medium surface with more sustained eupatilin release compared to the non-floating control tablet. X-ray photographs in beagle dogs showed that IPAPFR was retained for > 2 h in the stomach. In the ethanol-induced gastric ulcer rat model, the gastric hemorrhagic lesion was improved more substantially with IPAP-FR compared to the non-floating control tablet. Based on these data, our data suggest that IPAP-FR has an improved therapeutic potential for the treatment of gastric ulcer. [Mh] Termos MeSH primário: Artemisia/química Mucosa Gástrica/efeitos dos fármacos Extratos Vegetais/farmacologia [Mh] Termos MeSH secundário: 2-Propanol Animais Antiulcerosos/farmacologia Cães Etanol/efeitos adversos Flavonoides/farmacologia Indometacina/efeitos adversos Ligadura/efeitos adversos Masculino Úlcera Péptica Hemorrágica/induzido quimicamente Úlcera Péptica Hemorrágica/etiologia Úlcera Péptica Hemorrágica/prevenção & controle Extratos Vegetais/administração & dosagem Ratos Ratos Sprague-Dawley Úlcera Gástrica/induzido quimicamente Úlcera Gástrica/complicações Úlcera Gástrica/prevenção & controle Comprimidos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anti-Ulcer Agents); 0 (Flavonoids); 0 (Plant Extracts); 0 (Tablets); 3K9958V90M (Ethanol); 4D58O05490 (eupatilin); ND2M416302 (2-Propanol); XXE1CET956 (Indomethacin) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180131 [Lr] Data última revisão: 180131 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180117 [St] Status: MEDLINE

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[PMID]: 28449922 [Au] Autor: Genari B; Leitune VCB; Jornada DS; Camassola M; Arthur RA; Pohlmann AR; Guterres SS; Collares FM; Samuel SMW [Ad] Endereço: Dental Materials Laboratory, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: bruna.genari@ufrgs.br. [Ti] Título: Antimicrobial effect and physicochemical properties of an adhesive system containing nanocapsules. [So] Source: Dent Mater;33(6):735-742, 2017 06. [Is] ISSN: 1879-0097 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: OBJECTIVE: To incorporate indomethacin and triclosan-loaded nanocapsules into primer and adhesive, and evaluate its properties. METHODS: Indomethacin and triclosan were encapsulated by deposition of preformed polymer and subsequently characterized regarding morphology, particle size, drug content and cytotoxicity. Nanocapsules (NCs) were incorporated into primer at 2% and into adhesive at 1, 2, 5, and 10% concentrations. Degree of conversion (DC) and softening in ethanol of the adhesive were evaluated. Drug release and drug diffusion through dentin was quantified by high performance liquid chromatography. Antimicrobial test was performed until 96h. RESULTS: Spherical and biocompatible NCs presented mean size of 159nm. Drugs content was 3mg indomethacin/g powder and 2mg triclosan/g powder. Incorporating NCs in adhesive showed no influence in DC (p=0.335). The addition of 2% of NCs showed no influence in softening in ethanol (p>0.05). After 120h, 93% of indomethacin and 80% of triclosan were released from primer, 20% of indomethacin and 17% of triclosan were released from adhesive with 10% of NCs. Indomethacin showed diffusion through dentin. In 24h, adhesive containing 2 and 5% of NCs using primer with NCs showed antimicrobial effect. In 96h, adhesives containing different concentration of NCs promoted antimicrobial effect. CONCLUSIONS: Indomethacin and triclosan-loaded nanocapsules were successfully incorporated into primer and adhesive, promoting controlled drugs release, indomethacin diffusion through dentin and antimicrobial effect without compromising its physicochemical properties. SIGNIFICANCE: Indomethacin and triclosan-loaded nanocapsules have potential to prevent recurrent caries and to be used in deep cavities controlling pulpar inflammatory process. [Mh] Termos MeSH primário: Anti-Infecciosos Cimentos Dentários Nanocápsulas [Mh] Termos MeSH secundário: Dentina Indometacina [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anti-Infective Agents); 0 (Dental Cements); 0 (Nanocapsules); XXE1CET956 (Indomethacin) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180201 [Lr] Data última revisão: 180201 [Sb] Subgrupo de revista: D [Da] Data de entrada para processamento: 170429 [St] Status: MEDLINE

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[PMID]: 29223540 [Au] Autor: Luo C; Chen H; Wang Y; Lin G; Li C; Tan L; Su Z; Lai X; Xie J; Zeng H [Ad] Endereço: Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China. [Ti] Título: Protective effect of coptisine free base on indomethacin-induced gastric ulcers in rats: Characterization of potential molecular mechanisms. [So] Source: Life Sci;193:47-56, 2018 Jan 15. [Is] ISSN: 1879-0631 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: AIMS: The aim of this study was to comparatively investigate the potential gastroprotective effect and underlying mechanisms of coptisine free base (CFB, 8-hydroxy-7, 8-dihydrocoptisine), berberine and lansoprazole against indomethacin-induced gastric ulcer in rats. MATERIALS AND METHODS: CFB (10, 20 and 40mg/kg), berberine (20mg/kg) and lansoprazole (30mg/kg) were orally administrated to rats prior to indometacin ingestion, and gastric lesions were evaluated macroscopically and histologically, and further analyzed by ELISA, qRT-PCR and Western blot. KEY FINDINGS: CFB exerted comparable or superior gastroprotective effect to berberine in protecting against indomethacin-induced gastric injury. CFB pretreatment significantly enhanced the levels of superoxide dismutase (SOD) and glutathione (GSH), and markedly decreased the malonaldehyde (MDA) content. CFB administration effectively suppressed the levels of myeloperoxidase (MPO), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and angiotensin II (Ang II). Besides, CFB substantially up-regulated the mRNA expressions of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and promoted gastric mucosal prostaglandin E level (PGE ). Furthermore, CFB pretreatment remarkably increased the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) from cytosol into the nucleus, and the expression of heme oxygenase-1 (HO-1), while significantly decreased the expression of mitogen activated protein Kinase Kinase 6 (MKK6) and translocation of p38 mitogen-activated protein kinase (p38 MAPK). SIGNIFICANCE: This was the first investigation reporting the anti-ulcer effect of protoberberine alkaloid free base on in vivo rodent model. The gastroprotective mechanism of CFB might involve favorable regulation of antioxidant and anti-inflammatory status mediated, at least partially, by the Nrf2 signaling pathway and p38 MAPK translocation. [Mh] Termos MeSH primário: Berberina/análogos & derivados Úlcera Gástrica/tratamento farmacológico [Mh] Termos MeSH secundário: Animais Anti-Inflamatórios/farmacologia Antioxidantes/farmacologia Berberina/metabolismo Berberina/farmacologia Berberina/uso terapêutico Ciclo-Oxigenase 1/metabolismo Ciclo-Oxigenase 2/metabolismo Modelos Animais de Doenças Mucosa Gástrica/patologia Indometacina Interleucina-1beta/metabolismo Lansoprazol/farmacologia Lansoprazol/uso terapêutico Masculino Ratos Úlcera Gástrica/patologia Superóxido Dismutase/metabolismo Fator de Necrose Tumoral alfa/metabolismo Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anti-Inflammatory Agents); 0 (Antioxidants); 0 (Interleukin-1beta); 0 (Tumor Necrosis Factor-alpha); 0GCL71VN14 (coptisine); 0I8Y3P32UF (Berberine); 0K5C5T2QPG (Lansoprazole); EC 1.14.99.1 (Cyclooxygenase 1); EC 1.14.99.1 (Cyclooxygenase 2); EC 1.15.1.1 (Superoxide Dismutase); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); XXE1CET956 (Indomethacin) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180108 [Lr] Data última revisão: 180108 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171211 [St] Status: MEDLINE

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[PMID]: 28681929 [Au] Autor: Amanullah A; Mishra R; Upadhyay A; Reddy PP; Das R; Mishra A [Ad] Endereço: Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan, India. [Ti] Título: Indomethacin elicits proteasomal dysfunctions develops apoptosis through mitochondrial abnormalities. [So] Source: J Cell Physiol;233(2):1685-1699, 2018 Feb. [Is] ISSN: 1097-4652 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of drugs that are mainly used to treat pain, inflammation, and fever via cyclooxygenase-2 (COX-2) inhibition. There are abundant findings that uncover the hidden critical chemotherapeutics potential of NSAIDs in cancer treatment. However, still the precise mechanism by which NSAIDs could be used as an effective anti-tumor agent in the prevention of carcinogenesis is not well understood. Here, we show that indomethacin, a well-known NSAID, induces proteasomal dysfunction that results in accumulation of unwanted proteins, mitochondrial abnormalities, and successively stimulate apoptosis in cells. We observed the interaction of indomethacin with proteasome and noticed the massive accumulation of intracellular ubiquitin-positive proteins, which might be due to the suppression of proteasome activities. Furthermore, we also found that exposure of indomethacin causes the accumulation of critical proteasomal substrates that consequently generate severe mitochondrial abnormalities and prompt up key apoptotic events in cells. Our results demonstrate how indomethacin affects normal proteasomal functions and induces mitochondrial apoptosis in cells. These findings also improve our current understanding of how NSAIDs can exhibit crucial anti-proliferative effects in cells. In near future, our findings may suggest a new possible strategy for the development of specific proteasome inhibitors in conjunction with other chemo-preventive anticancer agents. [Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/farmacologia Antineoplásicos/farmacologia Apoptose/efeitos dos fármacos Indometacina/farmacologia Neoplasias Pulmonares/tratamento farmacológico Mitocôndrias/efeitos dos fármacos Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos Inibidores de Proteassoma/farmacologia [Mh] Termos MeSH secundário: Células A549 Animais Anti-Inflamatórios não Esteroides/química Antineoplásicos/química Células COS Cercopithecus aethiops Relação Dose-Resposta a Droga Seres Humanos Indometacina/química Neoplasias Pulmonares/enzimologia Neoplasias Pulmonares/patologia Mitocôndrias/metabolismo Mitocôndrias/patologia Simulação de Acoplamento Molecular Complexo de Endopeptidases do Proteassoma/química Complexo de Endopeptidases do Proteassoma/metabolismo Inibidores de Proteassoma/química Agregados Proteicos Ligação Proteica Proteólise Transdução de Sinais/efeitos dos fármacos Relação Estrutura-Atividade Fatores de Tempo Ubiquitinação [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Antineoplastic Agents); 0 (Proteasome Inhibitors); 0 (Protein Aggregates); EC 3.4.25.1 (Proteasome Endopeptidase Complex); XXE1CET956 (Indomethacin) [Em] Mês de entrada: 1711 [Cu] Atualização por classe: 171128 [Lr] Data última revisão: 171128 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170707 [St] Status: MEDLINE [do] DOI: 10.1002/jcp.26081

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MEDLINE

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[PMID]: 29061261 [Au] Autor: Buxbaum J; Yu CY [Ad] Endereço: Division of Gastroenterology, University of Southern California, Keck School of Medicine, Los Angeles, California, USA. [Ti] Título: Indomethacin and lactated Ringer's hydration to prevent post-ERCP pancreatitis: right combination but wrong volume. [So] Source: Gastrointest Endosc;86(5):925-926, 2017 11. [Is] ISSN: 1097-6779 [Cp] País de publicação: United States [La] Idioma: eng [Mh] Termos MeSH primário: Indometacina Pancreatite/prevenção & controle [Mh] Termos MeSH secundário: Colangiopancreatografia Retrógrada Endoscópica Seres Humanos [Pt] Tipo de publicação: LETTER; COMMENT [Nm] Nome de substância: XXE1CET956 (Indomethacin) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171031 [Lr] Data última revisão: 171031 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171025 [St] Status: MEDLINE

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